title: Censoring of self-reactive B cells by follicular dendritic cell-displayed self-antigen.
abstract: In the secondary lymphoid organs, intimate contact with follicular dendritic cells (FDCs) is required for B cell retention and Ag-driven selection during the germinal center response. However, selection of self-reactive B cells by Ag on FDCs has not been addressed. To this end, we generated a mouse model to conditionally express a membrane-bound self-antigen on FDCs and to monitor the fate of developing self-reactive B cells. In this article, we show that self-antigen displayed on FDCs mediates effective elimination of self-reactive B cells at the transitional stage. Notwithstanding, some self-reactive B cells persist beyond this checkpoint, showing evidence of Ag experience and intact proximal BCR signaling, but they are short-lived and unable to elicit T cell help. These results implicate FDCs as an important component of peripheral B cell tolerance that prevents the emergence of naive B cells capable of responding to sequestered self-antigens.
authors.affiliation: Program on Inflammatory Diseases, Sanford-Burnham Medical Research Institute, La Jolla, CA 92037, USA.
authors.forename: Irene W
authors.initials: IW
authors.lastname: Yau
authors.forename: Matthew H
authors.initials: MH
authors.lastname: Cato
authors.forename: Julia
authors.initials: J
authors.lastname: Jellusova
authors.forename: Tatiana
authors.initials: T
authors.lastname: Hurtado de Mendoza
authors.forename: Robert
authors.initials: R
authors.lastname: Brink
authors.forename: Robert C
authors.initials: RC
authors.lastname: Rickert
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D000936:Antigen-Antibody Complex / Q000276:immunology; D017209:Apoptosis / Q000276:immunology; D001324:Autoantigens / Q000276:immunology*; D015551:Autoimmunity; D001402:B-Lymphocytes / Q000276:immunology*; D049109:Cell Proliferation; D002478:Cells, Cultured; D020566:Dendritic Cells, Follicular / Q000276:immunology*; D008213:Lymphocyte Activation; D051379:Mice; D008822:Mice, Transgenic; D011947:Receptors, Antigen, B-Cell / Q000378:metabolism; D015398:Signal Transduction / Q000276:immunology
chemical_list: D000936:Antigen-Antibody Complex; D001324:Autoantigens; D011947:Receptors, Antigen, B-Cell